This invention relates to N-(arylalkyl) dibenzoxepin propanamine derivatives having useful antihistaminic activity with a low potential for sedation.
The utility of antihistamine compounds (histamine --H.sub.1 antagonists) as a treatment for the alleviation of the symptoms of allergic disorders has been long recognized. However, due to their effects on the central nervous system, numerous side effects are observed with these agents, most notably sedation (Douglas, W. W. In: "The Pharmacological Basis of Therapeutics," 6th ed; Gilman, A. G.; Goodman, L. S.; Gilman, A.; Ed.; Macmillian: New York, 1980; pp. 622-632). For example, the tricyclic antidepressant doxepin (3-dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-1-propanamine) is a potent antagonist of histamine --H.sub.1 receptors, but is known to cause sedation (Figge, J.; Leonard, P.; Richelson, E. Eur. J. Pharm., 1979, 58 479-483). Because of its activity in the central nervous system, the use of doxepin in the treatment of allergic disorders has been limited to topical treatment (Bernstein, J. E.; Endicott, C. J. Eur. Pat. Appl. EP93373 Al; CA, 100, 39611h and Bernstein, J. E. U.S. Pat. No. 4,395,420; CA, 99, 128371h).